SMALL ANIMAL IMAGING SHARED RESOURCE (SAISR) ABSTRACT The Small Animal Imaging Shared Resource (SAISR) provides instrumentation, training, and expert support for imaging studies conducted by UCLA Jonsson Comprehensive Cancer Center (JCCC) investigators. Major technologies and services include micro-positron emission tomography (microPET), invented at SAISR, micro- computed tomography (microCT), optical imaging (bioluminescence, fluorescence and Cerenkov), autoradiography imaging, and routine production of small molecule radiochemistry and peptide/protein radiolabeling. SAISR has a biomedical cyclotron, biomolecule radiolabeling facility, and a fully equipped radiochemistry facility with state-of-the-art radiosynthesizers specifically designed to support PET imaging. Three specific aims support the SAISR objective of providing investigators with technical imaging expertise and facilitating the design, execution, and analysis of small animal imaging studies. Aim 1: to provide and support state-of-the-art small animal imaging technologies; Aim 2: to provide routine radiochemistry and radiolabeling production services; and Aim 3: to provide investigators with scientific support and training in radiochemistry, preclinical imaging, and image analysis. Monthly two-hour training sessions educate users on the latest imaging technologies and approaches, including topics on instrumentation basics, imaging biology, imaging procedures, and safety protocols. Examples of SAISR impact in the prior project period include SAISR support for David Nathanson, PhD (CMINT) in developing novel combination therapies to target tumor metabolism in glioblastoma multiforme (GBM). PET/CT imaging of rapid changes in GBM glucose utilization by [18F]FDG, a biomarker of glycolysis, effectively predict therapeutic responses in vivo and is currently being tested in a clinical trial (NCT03732352). PET and MRI imaging enabled a large inter-programmatic team led by Robert Prins, PhD (CMINT/TI) to differentiate inflammatory responses in GBM by PET from other sources of contrast-enhancement seen by MRI. The combination of these two imaging modalities distinguished tumor progression from pseudoprogression in immunotherapy. In a collaboration between SAISR and JCCC Molecular Screening Shared Resource (MSSR), an inter-programmatic team led by Caius Radu, MD (CMINT) developed a combination therapy targeting deoxycytidine kinase (dCK) using [18F]FAC PET to assess the pharmacodynamics of novel dCK inhibitors. Follow-on PET studies showed that dCK contributes to radiation resistance in cancer. From 2013 ? 2018, SAISR supported projects from 42 JCCC members in all six Programs, representing 84% of SAISR usage. Of this, 53% of JCCC users had peer-reviewed funding. This resulted in 136 publications, with 73 (54%) in high-impact (IF ?10, or field leading) journals. The SAISR is preparing to submit an NIH shared instrumentation grant for a GNEXT PET/CT instrument, with the highest sensitivity currently available and based on technology invented by SAISR Director Arion Chatziioannou, PhD.